Optical weak measurement imaging detection system and method suitable for ultrahigh-precision antibiotic detection

Abstract

The invention discloses an optical weak measurement imaging detection system and method suitable for ultrahigh-precision antibiotic detection. The system comprises a light source, a first polarizer, a flow cell, a triangular prism, an achromatic quarter-wave slide, a second polarizer, an imaging lens, an image sensor and a data processing and analyzing module. According to the system, through pre-selection and post-selection of polarization states, total internal reflection occurs on the inner surface of the prism, and a phase difference between p polarization and s polarization is generated in reflected light, so that tiny disturbance of a sample to a light beam is amplified, and high-sensitivity detection is realized. The data processing module executes a weak measurement algorithm, analyzes signals of the image sensor, amplifies tiny physical quantity changes, and detects the content of target analytes such as antibiotics in the sample. The sensitivity of the sensing system to antibiotic micromolecules is remarkably improved, a new scheme is provided for unmarked optical sensing of target analytes such as antibiotic micromolecules, and the application field of optical weak measurement sensors can be greatly expanded.

Description

Technical Field

[0001] The present invention relates to label-free optical detection technology, and in particular to an optical weak measurement imaging detection system and method suitable for ultra-high precision antibiotic detection. Background Art

[0002] Since their discovery in the early 20th century, antibiotics have played a vital role in treating various bacterial infections. However, overuse or abuse of antibiotics can have harmful effects on human health. For example, chloramphenicol residues in animal-derived products can cause serious side effects. Therefore, sensitive and accurate determination of antibiotics is of great significance to public health. There are currently a variety of analytical techniques for antibiotic detection, typical representatives of which include high performance liquid chromatography, spectroscopy, electrochemical detection, isothermal titration microcalorimetry, and various new biosensors.

[0003] High performance liquid chromatography is based on the difference in relative affinity between different components in the mobile phase (solvent) and the stationary phase (chromatographic column filler). By controlling the flow rate, composition and properties of the solvent and the chromatographic column, the components in complex samples can be effectively separated. However, this technology has major limitations, such as high equipment costs, strict operation and maintenance requirements, and the selection of chromatographic columns and optimization of mobile phases require expertise and experience. In addition, for extremely complex samples or extremely low concentrations of analytes, complex and time-consuming pretreatment techniques or detectors may be required.

[0004] Spectroscopic methods are based on the interaction between matter and electromagnetic radiation (light), and are typically represented by UV-visible absorption spectroscopy and fluorescence spectroscopy. For small biological molecules, especially those with conjugated systems, such as aromatic amino acids in certain vitamins and proteins, UV-visible absorption spectroscopy is a commonly used detection and quantification method. Its principle is based on the transition of electrons inside molecules from the ground state to the excited state after absorbing light energy of a specific wavelength. This process is manifested as an absorption peak at a specific wavelength in the spectrum. However, the resolution of UV-visible absorption spectroscopy is relatively low, and its ability to separate components in complex samples is limited. It is often necessary to combine separation techniques such as chromatography to improve the accuracy and specificity of the analysis. For molecules without obvious UV or visible light absorption characteristics, this method cannot be directly applied, and a derivatization step is usually required to increase the sensitivity of detection.

[0005] Fluorescence spectroscopy is applicable to biological small molecules that naturally have fluorescent properties or molecules labeled with fluorescent dyes. The core of this technology is that when a molecule absorbs light energy of a certain wavelength, the electrons transition from the ground state to the excited state, and then when the electrons fall back to the ground state or the low-energy excited state, they release energy, part of which is emitted in the form of fluorescence. Fluorescence spectroscopy is simple to operate and can be used to track biological processes in real time. However, background fluorescence and fluorescence of other components in the sample will interfere with the results. Fluorescence intensity is greatly affected by factors such as the concentration of fluorescent molecules, solvent environment, pH value and temperature, so the experimental conditions need to be strictly controlled. For non-fluorescent biological small molecules, indirect detection is required through fluorescent labeling or combination with fluorescent probes, which increases the complexity of the operation and the cost of the experiment.

[0006] Electrochemical detection is an analytical technique based on electrochemical reactions. Common electrochemical detection methods include cyclic voltammetry, electrochemical impedance spectroscopy, etc. The core principle of this method is to measure the current changes associated with the redox reaction of biological small molecules on the electrode surface. The size of the current signal is proportional to the concentration of the biological small molecules, and quantitative analysis can be achieved through the standard curve. However, for non-electroactive or weakly electroactive biological small molecules, it is often necessary to enhance their electrical signals through chemical modification or the use of catalysts. Contamination of the electrode surface and the choice of electrode materials can also affect the stability and repeatability of the measurement. When dealing with complex samples, this technology often requires additional complex sample pretreatment steps to eliminate matrix effects.

[0007] Isothermal titration microcalorimetry is an experimental technique for accurately measuring heat changes in chemical reactions. This technique is not only suitable for studying macromolecules, but can also be used to detect interactions between small biological molecules and the binding between small molecules and macromolecules. This technique obtains the thermodynamic parameters of the reaction, such as binding constants, enthalpy changes, and entropy changes, by accurately measuring the heat changes generated as the reactants are gradually added to the sample cell under isothermal conditions. However, when it comes to small molecules with low concentrations, the sensitivity and accuracy of the detection may be challenged because the heat changes generated by the interactions between small molecules are small, which requires more sophisticated experimental design and operation to ensure reliable data. Isothermal titration microcalorimetry experiments are usually time-consuming, have high requirements on instruments, and the data analysis is relatively complex.

[0008] Biosensors are usually composed of biological recognition elements and signal conversion elements, which can convert the recognition of biological molecules into measurable electrical signals, optical signals or chemical signals. For the detection of small molecules, common types of biosensors include enzyme-based sensors, nanomaterial-based sensors and optical sensors.

[0009] Enzyme-based sensors use specific enzymes as biorecognition elements. Enzymes can specifically recognize target small molecules and catalyze chemical reactions. The products produced or the consumption of the reactions can be detected by electrochemical, optical, and other methods. Enzyme-based sensors are highly selective and sensitive and can detect specific small molecules in complex samples. However, the activity of enzymes may be affected by environmental factors (such as pH and temperature), resulting in poor stability and reproducibility.

[0010] Nanomaterial-based sensors use the unique physical, chemical, and biological properties of nanoscale materials to detect small biomolecules, including nanoparticles, nanotubes, nanobelts, and molecularly imprinted polymers. These nanomaterials are widely used in sensor development due to their high specific surface area, excellent electronic properties, and the ability to recognize specific biomolecules through surface modification. With the development of nanotechnology, nanomaterial-based sensors have shown extraordinary potential in clinical diagnosis, environmental monitoring, and food safety. However, nanomaterial-based sensors still face a series of challenges. The synthesis, functionalization, and sensor integration processes of nanomaterials are usually complex and costly, which limits their large-scale application. In addition, the stability and reliability of nanomaterials are also a major concern. Under different biological and environmental conditions, the chemical and physical properties of nanomaterials may change due to temperature, humidity, pH, or the presence of other chemicals. For example, nanoparticles may aggregate, changing their surface properties and reactivity, which may lead to attenuation or distortion of sensor signals.

[0011] Optical sensors include fluorescence, Raman scattering, interferometers, surface plasmon resonance (SPR), weak measurement sensors, etc. These sensors detect small molecules by detecting changes in optical properties (such as fluorescence intensity, wavelength change, absorbance change) caused by biorecognition events. The advantages of optical sensors are their non-invasiveness, high sensitivity and high selectivity, and they can be monitored in real time without destroying the sample. In addition, optical sensing technology is generally easy to operate, can achieve rapid detection, and is easy to implement remote and on-site detection. Among them, SPR sensors are a typical representative of existing antibiotic small molecule detection. The sensor monitors molecular interactions by detecting changes in the resonance conditions of surface plasmon waves on metal surfaces (usually gold or silver). When small molecules bind to ligands (such as proteins) fixed on the sensor surface, changes in the local refractive index cause changes in the resonance angle. This change can be detected by measuring changes in the intensity of reflected light, thereby achieving real-time, label-free and highly sensitive monitoring of small molecule-protein interactions. The main disadvantages of SPR biosensors include their expensive metal coating, the complexity of sample preparation and surface modification, and high sensitivity to environmental conditions such as temperature and ionic strength, which may affect the accuracy and reliability of the results.

[0012] Due to the small molecular size and relatively simple surface chemical properties of antibiotic small molecules, they face a key challenge in practical detection: at low concentrations, the signal response generated by traditional antibiotic detection techniques is usually weak. This is especially important because the content of antibiotics in food, environmental or clinical samples is often low. In addition, the detection signal is easily interfered by various types of noise, including experimental environment and equipment errors, which further reduces the reliability and detectability of the signal. Current detection methods are facing significant challenges, especially in terms of sensitivity, accuracy and ease of operation. Therefore, it is urgent to develop new detection methods to meet these challenges.

[0013] It should be noted that the information disclosed in the above background technology section is only used for understanding the background of the present application, and therefore may include information that does not constitute prior art known to ordinary technicians in the field. Summary of the invention

[0014] The main purpose of the present invention is to solve the problems existing in the above-mentioned background technology and to provide an optical weak measurement imaging detection system and method suitable for ultra-high precision antibiotic detection.

[0015] To achieve the above object, the present invention adopts the following technical solutions:

[0016] An optical weak measurement imaging detection system suitable for ultra-high precision antibiotic detection, comprising:

[0017] A light source, used to generate a broadband light source to provide an optical signal for the system;

[0018] A first polarizer, used to preselect the polarization direction of the light beam, by setting a predetermined polarization state as a preselected state to prepare the light beam for a subsequent weak interaction process;

[0019] a flow cell, arranged on one face of the prism, comprising an experimental flow channel and a reference flow channel, for injecting an experimental solution and a reference solution containing a sample to be measured, the experimental flow channel and the reference flow channel being arranged in parallel for synchronous real-time measurement, so that the sample interacts with the light beam;

[0020] A prism, used to achieve total internal reflection, thereby introducing a phase difference between p-polarization and s-polarization, wherein the phase difference will cause interference during the optical weak value amplification process, thereby amplifying a small disturbance of the light beam and introducing phase information for weak value extraction in the light beam;

[0021] An achromatic quarter glass, located between the prism and the second polarizer, is used to introduce a set phase delay to further modulate the polarization state of the light beam;

[0022] A second polarizer, used for post-selecting the polarization direction of the light beam, and completing post-selection in optical weak measurement by setting another predetermined polarization state as a post-selection state;

[0023] An imaging lens, used to focus the light beam modulated by the sample onto an imaging surface;

[0024] Image sensor, used to capture focused light signals and convert them into electrical signals;

[0025] The data processing and analysis module is used to process the signals collected by the image sensor, execute the weak measurement imaging detection algorithm, perform the pre-selected state, post-selected state and weak value amplification calculation of optical weak measurement, and amplify the tiny changes in physical quantities by calculating the weak values ​​between the pre-selected state and the post-selected state, thereby achieving ultra-high precision detection of target analytes such as antibiotics in the sample.

[0026] Furthermore, it also includes a collimating lens group and an achromatic beam expander located sequentially between the light source and the first polarizer. The collimating lens group includes a lens and an aperture, which are used to collimate the light emitted by the light source into parallel light, and the achromatic beam expander is used to expand the light beam.

[0027] Furthermore, the light source is a red LED.

[0028] Furthermore, the spectral wave function f(ω) of the light source is a Gaussian function:

[0029]

[0030] Among them, ω is the angular frequency variable, ω0 is the central angular frequency of the LED light source, Δ is a measure of the width of the wave function in the frequency domain, which is directly related to the spectral width of the LED, A is a normalization constant, and the total probability of the wave function integrated over the entire frequency domain is 1.

[0031] Furthermore, the polarization directions of the first polarizer and the second polarizer are adjusted to precisely control the polarization states of the pre-selected state and the post-selected state, so that the polarization directions of the two are close to orthogonal to meet the conditions for generating optical weak measurements; according to the Fresnel theorem, the angle at which the light beam enters the prism is adjusted to produce a predetermined phase difference, thereby achieving effective modulation between p-polarization and s-polarization in the reflected light; an initial phase delay is introduced using an achromatic quarter glass to modulate the polarization state of the light beam and optimize the phase distribution of the light beam after passing through the system; by adjusting the coupling strength and the optical frequency, the optimal performance of the system in the weak coupling state is achieved, ensuring that the change of the physical quantity to be measured can be effectively amplified between the pre-selected state and the post-selected state; by adjusting the setting of the post-selected state, the system is able to perform measurements within a high-sensitivity linear detection range to achieve ultra-high precision detection of target analytes in the sample.

[0032] Further, the pre-selected state is set: the first polarizer is adjusted to define the pre-selected polarization state of the light beam, thereby forming the initial polarization state of the light beam, and the polarization direction can be accurately set according to the experimental requirements; the phase difference is introduced: the total internal reflection characteristics of the prism are used to generate a predetermined phase difference between the p-polarization and s-polarization of the light beam, and the phase difference is determined according to the Fresnel theorem; the polarization state is modulated: the initial phase delay is introduced by the achromatic quarter glass, and the polarization direction of the incident light and the optical axis direction of the glass are controlled to facilitate accurate modulation of the polarization state of the light; the post-selected state is set: the post-selected state is set by the second polarizer , ensuring that the state is nearly orthogonal to the pre-selected state to complete the post-selection step of optical weak measurement; the data processing and analysis module is configured to perform the following steps of the weak measurement algorithm: calculate weak value amplification: based on the pre-selected state and the post-selected state, calculate the weak value in the system to amplify and detect tiny changes in physical quantities; determine the linear detection interval: analyze the light signal captured by the image sensor and determine the high-sensitivity linear detection interval so as to perform measurements within the interval; data processing: process and analyze the signals collected by the image sensor to achieve ultra-high precision detection of target analytes such as antibiotics in the sample.

[0033] Furthermore, the weak value in the system is calculated according to the following formula:

[0034]

[0035] Among them A ω represents a weak value, <ψ f | represents the conjugate transpose of the post-selected state, A represents the polarization operator, |ψ i > represents the pre-selected state, <ψ f |ψ i > represents the inner product between the post-selection state and the pre-selection state, ε represents the degree to which the angle between the post-selection state and the pre-selection state is close to orthogonal, represents the phase difference, i is the imaginary unit, and represents the unitary nature of the operator.

[0036] Further, the relative light intensity I and phase difference are determined according to the following formula: The approximate linear relationship between:

[0037]

[0038] Among them, ω represents the angular frequency, d represents the differential, ξ represents the quantum state, τ represents the coupling strength, Δ represents the measure of the width of the wave function in the frequency domain, ω0 represents the central angular frequency of the light source, and e represents the base of the natural logarithm.

[0039] Furthermore, the image sensor is a CMOS camera.

[0040] An optical weak measurement imaging detection method, using the optical weak measurement imaging detection system to perform ultra-high precision detection of target analytes;

[0041] Preferably, the target analyte comprises an antibiotic;

[0042] Preferably, the detection method comprises the following steps:

[0043] The bovine serum albumin conjugate of antibiotic small molecule D was modified on the surface of the prism, denoted as D-BSA, as a biorecognition element;

[0044] A solution of monoclonal antibody D-mAb containing antibiotic small molecule D is prepared;

[0045] The antibiotic small molecule D in the sample competes with D-BSA and D-mAb for binding, wherein the amount of D-BSA modified on the prism surface and the amount of D-mAb in the solution are kept constant;

[0046] The concentration of antibiotic small molecule D in the sample is quantitatively detected by measuring the signal change generated by the change in the specific binding amount of D-mAb and D-BSA.

[0047] The present invention has the following beneficial effects:

[0048] The present invention proposes a new type of ultra-high precision antibiotic small molecule sensing scheme based on optical weak measurement, which has the unique advantages of simplicity, real-time, sensitivity, low cost, and no labeling, and can be used to quickly detect antibiotic residues in food. Preferably, by introducing an indirect competitive inhibition test, the detection of ultra-low concentration antibiotic small molecules can be achieved. In an experiment taking chloramphenicol as an example, a chloramphenicol linear detection range of 6.46 to 9.70 ng / mL was obtained, and its concentration resolution was 33.20 pg / mL. This sensing scheme does not weaken the specificity, and the specificity still depends on the specificity of the antibody. At the same time, the scheme is also applicable to the detection of similar small molecules such as tetracycline, gibberellin, penicillin, and aflatoxin. The method was successfully used in the spiked test of chloramphenicol content in milk using chloramphenicol as an example. In short, this sensor based on optical weak measurement provides an effective strategy for label-free optical sensing of target analytes such as antibiotic small molecules, and expands the application field of sensors based on optical weak measurement.

[0049] The present invention proposes for the first time an ultra-high precision antibiotic sensing scheme based on optical weak measurement, which significantly improves the sensitivity of the sensing system to target analytes such as antibiotic small molecules. The present invention provides a new scheme for label-free optical sensing of target analytes such as antibiotic small molecules, which can greatly expand the application field of optical weak measurement sensors.

[0050] Other beneficial effects of the embodiments of the present invention will be further described below. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 The detection system of the embodiment of the present invention is shown, based on the chloramphenicol detection schematic diagram of the indirect competitive inhibition test. The interaction between chloramphenicol, chloramphenicol antibody and chloramphenicol-bovine serum albumin fixed on the sensor chip is described. When there is free chloramphenicol in the solution, it can inhibit the specific binding of antibody and chloramphenicol-bovine serum albumin, resulting in a reduction in the number of sensing interface antibodies and chloramphenicol-bovine serum albumin binding.

[0052] Figure 2 A physical diagram of an optical weak measurement imaging detection system according to an embodiment of the present invention is shown.

[0053] Figure 3 Shown are: (a) component structure diagram of the homemade light source; (b) component structure diagram of the homemade sensor detection module.

[0054] Figure 4 The relative light intensity changes corresponding to different concentrations of NaCl solutions are shown.

[0055] Figure 5 A linear fit graph of the relative light intensity change and the refractive index is shown.

[0056] Figure 6 Shown are: (a) AFM image of a glass slide without any surface treatment; (b) AFM image of a glass slide modified with a polydopamine coating; (c) AFM three-dimensional imaging of a glass slide without any surface treatment (left) and a glass slide modified with a polydopamine coating (right); (d) the surface height distribution at the blue dotted line in (a); (e) the surface height distribution at the red dotted line in (b).

[0057] Figure 7 The electron microscopy characterization of the polydopamine coating modification step is shown. The electron microscopy images of the prism surface without any surface treatment are shown in (a) and (b), (a) and (b) are different regions of the same prism; the electron microscopy images of the prism after polydopamine coating modification are shown in (c) and (d), (c) and (d) are different regions of the same prism.

[0058] Figure 8 The figure shows the modification process of the experimental flow channel and the reference flow channel in the sensor chip.

[0059] Fig. 9The following are shown: (a) relative light intensity changes of the experimental and reference channels in the chip when the CAP concentration is 10 ng / mL; (b) differential curve when the CAP concentration is 10 ng / mL; (c) calibration curve of CAP detected by indirect competitive inhibition test. The squares in the figure represent the average values ​​of the three sets of original measurement data, and their error bars are marked accordingly; the S-shaped curve is a fitting curve based on the Logistic mathematical model, and its determination coefficient (R 2 ) is 0.9938; the dotted line is the tangent of the fitting curve at the point of minimum slope, marking the point where the concentration responds most sensitively to changes in light intensity.

[0060] Fig.10 The variation curve of the coefficient of variation with the relative light intensity is shown. The area with a coefficient of variation lower than 0.1 usually indicates that the data has very low relative dispersion, which is called the stability area; the area with a coefficient of variation greater than 0.1 usually reflects that the data has a large volatility and dispersion relative to its average value, which is called the high variation area in the present invention. In this area, the relative difference between the data points is large, indicating that the consistency of the data is low.

[0061] Fig.11 Shown are: (a) the difference curves of chloramphenicol, gibberellin and tetracycline at a concentration level of 5 ng / mL. (b) the relative light intensity changes caused by chloramphenicol (CAP), gibberellin (GA), penicillin (PCN), ofloxacin (OFLX) and cephalexin (CEX) on the same sensor chip.

[0062] Fig.12 Shown are: (a) the relative light intensity change between the experimental flow channel and the reference flow channel in the milk sample; (b) the difference curve of chloramphenicol content detection in the milk sample.

[0063] Reference numerals:

[0064] 1. Achromatic beam expander; 2. First polarizer; 3. Sensing module, including prism and flow cell, wherein the flow cell is composed of experimental flow channel and reference flow channel; 4. Achromatic quarter glass; 5. Second polarizer; 6. Imaging lens; 7. CMOS camera. DETAILED DESCRIPTION

[0065] The following is a detailed description of the embodiments of the present invention. It should be emphasized that the following description is only exemplary and is not intended to limit the scope and application of the present invention.

[0066] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element. In addition, connection can be used for fixing as well as for coupling or communication.

[0067] It should be understood that the orientation or position relationship indicated by terms such as "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing the embodiments of the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.

[0068] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the embodiments of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0069] The concept of optical weak measurement was first proposed by Aharonov, Albert and Vaidman in 1988. This theory describes a process involving three key steps: first, the quantum system collapses to the same state after a strong measurement, called the pre-selected state; then, the physical quantity to be measured causes a perturbation to the system, causing a weak coupling between the quantum system and the detection instrument. This coupling is weak enough that the system is still in the pre-selected state after coupling, and will not cause the collapse of the quantum system, thus avoiding small interference and the loss of the physical quantity state. Finally, another strong measurement is performed on the system to cause it to collapse to another state, called the post-selected state. In this process, when the pre-selected state and the post-selected state are close to orthogonal, the measuring instrument will collect an abnormal result, called a weak value. This weak value may far exceed the general range of the system's eigenvalues, forming a weak value amplification effect. This effect provides a new strategy for measuring extremely small physical quantities. By introducing weak measurement technology, the detection accuracy of classical interferometry can be improved by 2 to 3 orders of magnitude, which is a subversive improvement. It has been widely used in the measurement of tiny parameters, such as the spin Hall effect of light, single-photon nonlinear effects, etc.

[0070] The embodiment of the present invention proposes for the first time an ultra-high precision antibiotic sensing scheme based on optical weak measurement, which significantly improves the sensitivity of the sensing system to antibiotic small molecules. The present invention provides a new scheme for label-free optical sensing of target analytes such as antibiotic small molecules, which can greatly expand the application field of optical weak measurement sensors.

[0071] See also Figure 1 , an optical weak measurement imaging detection system suitable for ultra-high precision antibiotic detection, comprising: a light source, preferably a red light LED, for generating a broadband light source to provide an optical signal for the system; a first polarizer 2, for pre-selecting the polarization direction of the light beam, by setting a predetermined polarization state as a pre-selected state to prepare the light beam for a subsequent weak interaction process; a sensing module 3, comprising a prism and a flow cell; the flow cell is arranged on one surface of the prism, comprising an experimental flow channel and a reference flow channel, for injecting an experimental solution containing a sample to be tested and a reference solution, the experimental flow channel and the reference flow channel are arranged in parallel for synchronous real-time measurement, so that the sample interacts with the light beam; the prism is connected to the flow cell, for achieving total internal reflection, thereby introducing a phase difference between p-polarization and s-polarization, the phase difference will cause interference in the process of optical weak value amplification, thereby amplifying a small disturbance of the light beam and introducing phase information for weak value extraction in the light beam; an achromatic quad A first-half glass slide 4 is located between the prism and the second polarizer 5, and is used to introduce a set phase delay to further modulate the polarization state of the light beam; the second polarizer 5 is used to post-select the polarization direction of the light beam, and completes the post-selection in the optical weak measurement by setting another predetermined polarization state as the post-selection state; an imaging lens 6 is used to focus the light beam modulated by the sample onto the imaging surface; an image sensor, preferably a CMOS camera 7, is used to capture the focused light signal and convert it into an electrical signal, and the captured light signal includes but is not limited to the intensity, polarization state and phase information of the light; a data processing and analysis module (not shown) is used to process the signal collected by the image sensor, execute the weak measurement imaging detection algorithm, and perform pre-selection state, post-selection state and weak value amplification calculation of the optical weak measurement, and amplify the tiny physical quantity changes by calculating the weak value between the pre-selection state and the post-selection state, thereby achieving ultra-high precision detection of target analytes such as antibiotics in the sample.

[0072] In a preferred embodiment, the optical weak measurement imaging detection system also includes a collimating lens group and an achromatic beam expander 1 which are sequentially located between the light source and the first polarizer. The collimating lens group includes a lens and an aperture for collimating the light emitted by the light source into parallel light, and the achromatic beam expander is used to achromatically expand the light beam.

[0073] In some embodiments, an optical weak measurement imaging detection method uses the optical weak measurement imaging detection system to perform ultra-high precision detection of target analytes, wherein the target analytes include antibiotic small molecules.

[0074] The specific embodiments of the present invention are further described below.

[0075] Optical weak measurement imaging detection system such as Figure 1 As shown. The red light generated by the light-emitting diode (LED, LR W5AP, Osram, central wavelength λ0 = 632.8nm, power P = 5W) is collimated into parallel incident light after passing through (GCO-2104, 25×, Daheng Optics), an aperture (diameter φ = 0.3nm) and a double-cemented achromatic lens (GCL-010652, focal length f = 50mm, Daheng Optics). The parallel light first passes through an achromatic beam expander (Thorlabs Inc., GBE05-B-5X AchromaticGalilean Beam Expander), and then is pre-selected by the first polarizer (Thorlabs Inc., LPVIS100-MP2, extinction ratio 100000:1), whose transmission axis is at an angle of 45° to the vertical direction. The light beam then undergoes total internal reflection on the inner surface of the ZF6 prism, generating a phase difference between p-polarization and s-polarization in the reflected light. After passing through an achromatic quarter glass (Thorlabs Inc., AQWP10M-580), the reflected light is selected by a second polarizer (Thorlabs Inc., LPVIS100-MP2, extinction ratio 100000:1). The selected light passes through a lens (Thorlabs Inc., AC508-300-AB-ML) and is finally collected by a CMOS camera (Thorlabs Inc., Kiralux 12.3MP Color CMOS Camera, USB 3.0Interface). The experimental sample is pumped into the flow channel by a syringe pump (Pump11, Harvard Apparatus, USA).

[0076] Using a red LED as a broadband light source, its spectral wave function f(ω) is expressed as a Gaussian function. The expression of f(ω) can be written as:

[0077]

[0078] Where ω is the angular frequency variable, ω0 is the central angular frequency of the LED light source, Δ is a measure of the width of the wave function in the frequency domain, which is directly related to the spectral width of the LED, and A is a normalization constant that ensures that the total probability of the wave function (integrated over the entire frequency domain) is 1.

[0079] The polarization direction of the polarizer is set to be consistent with the vertical direction, so its polarization state can be written as |H> and |V> are the horizontal and vertical polarization states respectively. Then, the light beam is incident on the inner surface of the prism at an angle greater than the critical angle θ0 of total reflection, introducing a certain phase difference between the p-wave and s-wave in the reflected light. According to Fresnel's theorem:

[0080]

[0081] Here, θ is the incident angle, n is the refractive index of the ZF6 prism, n = n1 / n2, n1 = 1.73, and n2 is the equivalent refractive index on the other side of the reflection interface. Therefore, the polarization state of the reflected light can be written as: Then, the light beam passes through an achromatic quarter-wave plate, whose fast axis direction makes an angle of π / 4 with the vertical direction, and the interaction between the light beam and the wave plate can be written as e iπ / 4(|H><V|-|V><H|) . Therefore, the preselected beam coupling state is:

[0082]

[0083] Weak coupling can be represented by a unitary operator U = e -iτAω , where τ is the coupling strength, ω is the optical frequency, and A is the polarization operator, satisfying the relation: A = -i|H><V| + i|V><H|. The state of the system after weak coupling can be written in the following form:

[0084]

[0085] The post-selection process is implemented by another polarizer. The post-selected state |ψ f > can be obtained by the following formula:

[0086]

[0087] where ε is a very small value, and the pre- and post-polarization states are nearly orthogonal. According to the weak value amplification theory, the weak value can be written as:

[0088]

[0089] When ε << 1 and The post-selection can amplify the offset of the central wavelength. By measuring the offset of the central wavelength to reflect the small physical quantity to be measured in the system, the highest sensitivity can be obtained in the approximately linear region. The relationship between the relative light intensity I collected by the CMOS camera and the phase difference is as follows:

[0090]

[0091] It can be determined from the above formula that there is a quadratic function relationship between the relative light intensity and the phase difference, and when measuring in a relatively small range, an approximate linear relationship can be obtained. The present invention names the above range as the "high-sensitivity linear detection interval".

[0092] For the detection application strategy, the preferred embodiment of the present invention adopts the strategy of indirect competitive inhibition test to achieve accurate detection of ultra-low concentrations of antibiotic small molecules. Specifically, the antibiotic small molecule D in the sample competes with the D-bovine serum albumin conjugate (D-BSA) modified on the prism surface for the monoclonal antibody (D-mAb) of D. The amount of D-BSA modified on the chip surface and the amount of D-mAb in the solution are kept constant. When the concentration of D in the sample is high, the specific binding of D-mAb to D-BSA is reduced. On the contrary, when the concentration of D in the sample is low, more antibodies can bind to D-BSA, forming a larger number of antibody and D-BSA complexes at the sensing interface. This method provides a highly sensitive and specific means of detecting antibiotic small molecules by accurately regulating and measuring changes in signals.

[0093] The flow cell consists of two identical, non-interconnected channels - an experimental channel and a reference channel. In specific experimental operations, the experimental flow channel is injected with an experimental solution containing the sample or reactant to be analyzed; while the reference flow channel is injected with a reference solution for calibration. The reference solution provides a baseline or standard for the experiment to facilitate the evaluation of biochemical reactions or changes in the experimental solution. Here, a D-mAb solution with the target removed is selected as a reference. Preferably, the differential calibration algorithm used can effectively correct or eliminate background noise and nonspecific signal interference in the test flow channel.

[0094] CMOS cameras can provide high spatial resolution imaging due to their high pixel density. This feature enables each pixel in the camera to act as an independent sensor unit. We fully utilized this advantage to average tens of thousands of pixels at each sampling point and record the average relative light intensity change, which is the statistically significant macroscopic result of the specific recognition process. This method not only effectively reduces noise interference, but also significantly improves the credibility of the signal.

[0095] Examples

[0096] 1. System resolution determination

[0097] In order to obtain the resolution of the optical weak measurement imaging detection system, different concentrations of NaCl solution were introduced to observe how the relative light intensity changes with the increase of NaCl solution concentration. In the experiment, the concentration of NaCl solution was set to 8g / L, 10g / L, 12g / L, 14g / L and 16g / L. In this study, 0.08g, 0.10g, 0.12g, 0.14g, and 0.16g of NaCl solid particles were weighed in turn on a balance and dissolved in 10mL of ultrapure water treated with a 0.22μm filter.

[0098] Next, the system dimming steps are introduced. First, the light beam is collimated. It should be noted that the imaging point is not as small as possible, but a uniform light spot that is constant at a distance. At the same time, the light beam is always parallel to the air flotation platform. Then, use the prism with the flow channel fixed and glued to adjust the angle of the incident light to just slightly larger than the total internal reflection angle. Remove the front and rear polarizers and achromatic quarter glass from the system, adjust the light to enter the CMOS camera, observe the change of the average relative light intensity in the flow channel area on the computer display, and slowly rotate the horizontal rotation axis of the prism. When the average light intensity in the flow channel is almost unchanged, the incident angle is just slightly larger than the total internal reflection angle. Finally, put in the removed optical element, rotate the achromatic quarter glass and the rear polarizer, and increase the average relative light intensity in the flow channel to 32000~35000 a.u. (relative light intensity unit). At this time, the system is in the optimal working range, and the optical element cannot be adjusted or rotated.

[0099] In the order of increasing concentration gradient, NaCl solution is introduced into the flow channel in sequence. In order to accurately control the refractive index change and other related variables caused by the flow of solution on the prism surface, after introducing each concentration of NaCl solution, it is necessary to wait for the solution in the flow channel to stabilize before collecting data on the relative light intensity change. Under room temperature conditions, the relationship between the refractive index n and the concentration of NaCl solution is: n = 1.3317 + 1.47 × 10 -3 C, C are mass percentages. The relative light intensity change δ caused by different concentrations of NaCl solution was calculated using the least squares method. I and the refractive index change δ n Perform linear fitting. The expression of the fitted line is: y = -9549666.67x + 12770233.50, R 2 =0.9977. The slope of the fitting line is I / δ n The absolute value of the refractive index sensitivity δ of the system s Therefore, the refractive index resolution σ of the proposed optical weak measurement imaging detection system r =3×σ s / (δ I / δ n )≈4.59×10 -7RIU (RIU is the refractive index unit).

[0100] 2. Chip modification steps

[0101] The flow cell is attached to the prism with epoxy resin adhesive, and the two together constitute the chip of the sensor. The solution flows over the surface of the equilateral prism through a flow cell with two channels. The flow channel array was drawn with SolidWorks and processed by 3D printing with resin material. The equilateral prism is made of ZF6 glass with a size of 27×27×27mm. Unless otherwise specified, the temperature of all experiments was room temperature (25℃) and the flow rate was 40μL / min. First, PBS solution was injected into the flow channel for 10min to obtain a stable baseline signal. Then, 1mg / mL dopamine solution was mixed with 10mM Tris-HCl buffer and injected into the flow channel to form a thin adhesion layer on the prism. It should be noted that dopamine is very easy to self-polymerize in Tris-HCl buffer, and this process will be significantly accelerated under aerobic and light conditions. Therefore, this mixed solution needs to be prepared on-site according to needs and must be stored under light-proof conditions.

[0102] After the polydopamine coating was modified, the flow channel was washed by injecting PBS solution for 1 min, and then PBS buffer containing 40μg / mL D-BSA was passed through at a flow rate of 30μL / min for 60min. This stage is crucial for the fixation of the biorecognition layer. After washing with PBS, a protein-free blocking solution was passed through the flow channel for 20min to block any unbound polydopamine sites to ensure specificity and minimize nonspecific binding. The modified chip was washed with PBS for several minutes to completely remove unbound molecules. Finally, the flow channel was sealed with PBS and stored at 4°C for subsequent experiments.

[0103] 3. Differential curve acquisition

[0104] To explore the quantitative relationship between the concentration of antibiotic small molecules and the change in relative light intensity, we used the concentration of D as the only variable and designed seven sets of concentration gradient experiments. First, PBS buffer was injected into the modified chip for 15 minutes. At this time, the average light intensity recorded by the CMOS camera will be used as the baseline for subsequent offset analysis. Subsequently, a mixed solution of D and D-mAb premixed at room temperature for 30 minutes was injected into the experimental channel for 2 hours, while only an antibody solution of equal concentration was injected into the reference channel. In all experiments, the concentration of D-mAb was constant at 1μg / mL. The final concentrations of D were 0, 5ng / mL, 6.667ng / mL, 8.333ng / mL, 10ng / mL, 15ng / mL, and 20ng / mL, respectively. Finally, PBS buffer solution flowed through both channels for 15 minutes. Assume that the number of D-BSA labels modified on the sensing interface in the experimental channel and the reference channel is γ, the number of antibodies used is α, and the concentration of D is β, where γ>>α, γ>>α-β. In optical weak measurement imaging sensors, as the specific binding process proceeds, the signal value decreases, so there is a negative correlation between the response and the specific binding number. - (R,β),β - (R,α-β), b + ,b - Indicates positive correlation and negative correlation, and R is the response value. Using the baseline of the above offset analysis, calculate the correction coefficient K between the experimental flow channel and the reference flow channel, and then draw a difference curve. In the difference curve, the response value corresponding to different concentrations is R d , which satisfies b - (R d ,|α-(α-β)|)=b - (R d ,|β|), which is consistent with the characteristics of sensor signal changes.

[0105] Practical application examples

[0106] Taking the detection of chloramphenicol (CAP) small molecules as an example, the feasibility experiment was verified according to the above steps. Focus on the light intensity fluctuations of about 20,000 pixels in the flow channel area in the image captured by the CMOS camera. By calculating the average light intensity of these selected pixels, the system noise is significantly reduced. The differential calibration method is used to eliminate additive noise, and the common nonspecific response can be well suppressed. Under each CAP concentration gradient, three different pixel areas are selected to calculate the relative light intensity changes, so as to obtain the error or uncertainty of each data point. By calculating the coefficient of variation of the three measurement results, it is found that the coefficient of variation of the data points shows regular differences with the change of CAP concentration. Specifically, the coefficient of variation of the five groups of experiments with CAP concentrations ranging from 0 to 10 ng / mL is less than 0.1, which is about 3.93%, 4.60%, 4.31%, 7.18%, and 8.13%, respectively, which reflects that the measurement data is relatively stable and the discreteness is small. When the CAP concentration is 15ng / mL and 20ng / mL, the coefficient of variation is calculated to be 16.25% and 28.34%, which indicates that the volatility of the data increases. This shows that the sensing scheme still has good stability and reproducibility within the linear measurement range. When the CAP concentration increases beyond the linear calculation range, the data stability deteriorates. This is because the number of antibodies remaining in the premixed solution after competition decreases, and the uniformity of binding at the sensing interface decreases, causing the results calculated in different sensing areas to fluctuate. By improving the modification method of the substrate chloramphenicol-bovine serum albumin conjugates (CAP-BSA) or using more sensing sites to participate in the calculation of the average, the coefficient of variation can be effectively avoided from being too large at high concentrations.

[0107] Next, a mathematical model based on the Logistic function was established to accurately describe this set of data showing saturation characteristics. In order to ensure the best fit between the model and the experimental data, the nonlinear least squares method was used to optimize the model parameters. The core of this method is to minimize the deviation between the model prediction value and the experimental measurement value. After fitting, an inverted S-shaped curve of relative light intensity changing with CAP concentration was obtained. The expression of the fitting curve is R 2=0.9938. At each specific CAP concentration, the CAP-BSA fixed on the surface of the sensor chip will specifically capture the free chloramphenicol monoclonal antibody (CAP-mAb) in the solution, causing a change in the refractive index of the prism surface. As the concentration of free CAP in the solution increases, the specific binding between CAP and CAP-mAb is relatively enhanced, thereby enhancing the inhibitory effect on the specific binding of the antibody to CAP-BSA. This competitive interaction leads to a decrease in the number of antibody-CAP-BSA conjugates formed, which in turn leads to a decrease in the result after differentiation.

[0108] Calculate the tangent of the fitting curve at its inflection point, this tangent is called the maximum slope tangent. The expression of the maximum slope tangent is y = -131.93x + 1574.83. It is the point where the absolute value of the slope of the fitting curve reaches the maximum value, that is, the position with the highest detection sensitivity. We calculate the deviation between the fitting curve and the maximum slope tangent, and find the interval where the deviation value is less than 5%. Thus, the high-sensitivity linear detection interval of the sensor is determined to be 6.46-9.70 ng / mL. The deviation of the relative light intensity change within 15 minutes of the baseline is calculated as the standard deviation of the system, and the standard deviation is 1.46 au (light intensity unit). According to equation C r =3×δ s / (ΔI / ΔC), where C r is the resolution of the sensor, δ s is the standard deviation of the system, ΔI is the change in relative light intensity, and ΔC is the change in CAP concentration. Therefore, the resolution of the optical weak measurement sensor is 33.20 pg / mL.

[0109] In order to study the versatility of the sensing scheme, in the application example of CAP detection, ultra-low concentration detection was performed on two other common antibiotics, tetracycline and gibberellin. Tetracycline and gibberellin are quite different from CAP in chemical structure and physical properties, which provides a good opportunity to verify the wide applicability of the sensor. The scheme of indirect competitive inhibition test was continued to be adopted, while ensuring the consistency of sensor parameters, chip modification steps, reagent concentration and experimental environment. The concentrations of gibberellin and tetracycline were both selected to be 5ng / mL. At the same concentration, the response values ​​and dynamic curves of gibberellin, tetracycline and chloramphenicol were different, which shows that the sensor can accurately detect and distinguish different antibiotics at extremely low concentration levels. Therefore, the sensing scheme proposed by the present invention is not limited to the detection of CAP content, but can be applied to the detection of different types of antibiotics. This feature makes the sensing scheme have important application prospects in the fields of environmental monitoring, food safety and medical research.

[0110] In order to verify the specific binding ability of the sensor when measuring a specific antibiotic small molecule, taking the detection of chloramphenicol as an example, several other common antibiotics were tested, such as gibberellins, penicillins, ofloxacin, etc., and the response signals of the sensing scheme were recorded under the same experimental environment. In this experiment, the above-mentioned antibiotic solutions were injected into the same modified CAP-BSA chip, and the response signals of the sensing scheme were recorded under the same experimental environment. When the sample is other antibiotics such as gibberellins, penicillins, ofloxacin, etc., the signal of the sensing system does not change significantly, and when the sample is CAP, the sensing scheme can capture significant signal changes. In summary, the results show that the sensing method proposed in the present invention can achieve ultra-high precision specific recognition of a selected detection target antibiotic.

[0111] Taking chloramphenicol as an example, the sensor of the present invention is used for the spiked test of milk. Milk is a complex biological liquid, mainly composed of water, fat, protein, lactose, vitamins and various minerals. The milk purchased from the market was centrifuged for 10 minutes, and the speed was set to 12000r / min. The supernatant was selected and diluted 10 times with PBS buffer, and CAP was added to form a 5ng / mL sample to be tested. Repeat the above experimental steps, perform pixel point averaging calculations on the three areas in the collected image, and then take the average value as the final data. After differential calibration, a relative light intensity change of 798.82au was obtained, which is very consistent with the above-mentioned chloramphenicol S-type detection curve, which confirms that the sensing scheme proposed by the present invention can be successfully used to detect whether milk contains trace amounts of CAP. The actual operation of other samples is similar.

[0112] In summary, the present invention proposes for the first time a sensing scheme for ultra-high precision target analytes, especially antibiotics, based on optical weak measurement. Preferably, the sensor introduces a strategy of indirect competitive inhibition test, which significantly improves the sensitivity of the sensing system to antibiotic small molecules. The preferred pixel average and differential calibration algorithm also ensures the high stability of the system. The present invention provides a new solution for label-free optical sensing of target analytes such as antibiotic small molecules, which greatly expands the application field of optical weak measurement sensors.

[0113] The above content is a further detailed description of the present invention in combination with specific / preferred embodiments, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, without departing from the concept of the present invention, it can also make several substitutions or modifications to these described embodiments, and these substitutions or modifications should be regarded as belonging to the protection scope of the present invention. In the description of this specification, the description of the reference terms "an embodiment", "some embodiments", "preferred embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in combination with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily target the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In the absence of mutual contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples. Although the embodiments of the present invention and their advantages have been described in detail, it should be understood that various changes, substitutions and modifications can be made herein without departing from the scope of protection of the patent application.

Claims

1. An optical weak measurement imaging detection system suitable for ultra-high precision antibiotic detection, characterized in that: include: A light source, used to generate a broadband light source to provide an optical signal for the system; A first polarizer, used to preselect the polarization direction of the light beam, by setting a predetermined polarization state as a preselected state to prepare the light beam for a subsequent weak interaction process; a flow cell, arranged on one face of the prism, comprising an experimental flow channel and a reference flow channel, for injecting an experimental solution and a reference solution containing a sample to be measured, the experimental flow channel and the reference flow channel being arranged in parallel for synchronous real-time measurement, so that the sample interacts with the light beam; A prism, used to achieve total internal reflection, thereby introducing a phase difference between p-polarization and s-polarization, wherein the phase difference will cause interference during the optical weak value amplification process, thereby amplifying a small disturbance of the light beam and introducing phase information for weak value extraction in the light beam; An achromatic quarter glass, located between the prism and the second polarizer, is used to introduce a set phase delay to further modulate the polarization state of the light beam; A second polarizer, used for post-selecting the polarization direction of the light beam, and completing post-selection in optical weak measurement by setting another predetermined polarization state as a post-selection state; An imaging lens, used to focus the light beam modulated by the sample onto an imaging surface; Image sensor, used to capture focused light signals and convert them into electrical signals; The data processing and analysis module is used to process the signals collected by the image sensor, execute the weak measurement imaging detection algorithm, perform the pre-selected state, post-selected state and weak value amplification calculation of optical weak measurement, and amplify the tiny changes in physical quantities by calculating the weak value between the pre-selected state and the post-selected state, thereby achieving ultra-high precision detection of the target analyte in the sample.

2. The optical weak measurement imaging detection system according to claim 1, characterized in that: It also includes a collimating lens group and an achromatic beam expander which are sequentially located between the light source and the first polarizer. The collimating lens group includes a lens and an aperture for collimating the light emitted by the light source into parallel light, and the achromatic beam expander is used for achromatically expanding the light beam.

3. The optical weak measurement imaging detection system according to claim 1 or 2, characterized in that: The light source is a red LED.

4. The optical weak measurement imaging detection system according to claim 3, characterized in that: The spectral wave function f(ω) of the light source is a Gaussian function: Among them, ω is the angular frequency variable, ω0 is the central angular frequency of the LED light source, Δ is a measure of the width of the wave function in the frequency domain, which is directly related to the spectral width of the LED, A is a normalization constant, and the total probability of the wave function integrated over the entire frequency domain is 1.

5. The optical weak measurement imaging detection system according to any one of claims 1 to 4, characterized in that: The polarization directions of the first polarizer and the second polarizer are configured to accurately control the polarization states of the pre-selected state and the post-selected state so that the polarization directions of the two are close to orthogonal to meet the generation conditions of the optical weak measurement; According to Fresnel's theorem, the angle at which the light beam enters the prism is adjusted to produce a predetermined phase difference, thereby achieving effective modulation between p-polarization and s-polarization in the reflected light; An achromatic quarter glass is used to introduce an initial phase delay to modulate the polarization state of the beam and optimize the phase distribution of the beam after it passes through the system; By adjusting the coupling strength and optical frequency, the optimal performance of the system in the weak coupling state is achieved, ensuring that the change of the physical quantity to be measured can be effectively amplified between the pre-selected state and the post-selected state; By adjusting the settings of the post-selection state, the system can perform measurements within the high-sensitivity linear detection range.

6. The optical weak measurement imaging detection system according to any one of claims 1 to 5, characterized in that: Setting a preselected state: adjusting the first polarizer to define a preselected polarization state of the light beam, thereby forming an initial polarization state of the light beam; Introducing phase difference: utilizing the total internal reflection property of the prism to generate a predetermined phase difference between the p-polarization and s-polarization of the light beam, which is determined according to the Fresnel theorem; Modulate the polarization state: introduce initial phase delay through the achromatic quarter glass, and control the polarization direction of the incident light and the optical axis direction of the glass to facilitate precise modulation of the polarization state of the light; Setting of post-selection state: Setting the post-selection state by a second polarizer to ensure that the state is nearly orthogonal to the pre-selection state, so as to complete the post-selection step of optical weak measurement; The data processing and analysis module is configured to perform the following steps of a weak measurement algorithm: Computational weak value amplification: Based on the pre-selected state and the post-selected state, the weak values ​​in the system are calculated to amplify and detect tiny changes in physical quantities; Determine the linear detection interval: Analyze the light signal captured by the image sensor and determine the high-sensitivity linear detection interval so that measurement can be performed within the interval; Data processing: The signals collected by the image sensor are processed and analyzed to achieve ultra-high precision detection of target analytes in the sample.

7. The optical weak measurement imaging detection system according to claim 6, characterized in that in, The weak value in the system is calculated according to the following formula: Among them A ω represents a weak value, <ψ f | represents the conjugate transpose of the post-selected state, A represents the polarization operator, |ψ i > indicates the pre-selected state, <ξ f |ψ i > represents the inner product between the post-selection state and the pre-selection state, ε represents the degree to which the angle between the post-selection state and the pre-selection state is close to orthogonal, represents the phase difference, i is the imaginary unit, and represents the unitary nature of the operator.

8. The optical weak measurement imaging detection system according to claim 7, characterized in that in, Determine the relative light intensity I and phase difference according to the following formula The approximate linear relationship between: Among them, ω represents the angular frequency, d represents the differential, ξ represents the quantum state, τ represents the coupling strength, Δ represents the measure of the width of the wave function in the frequency domain, ω0 represents the central angular frequency of the light source, and e represents the base of the natural logarithm.

9. The optical weak measurement imaging detection system according to any one of claims 1 to 8, characterized in that: The image sensor is a CMOS camera.

10. An optical weak measurement imaging detection method, characterized in that: Using the optical weak measurement imaging detection system as described in any one of claims 1 to 9 to perform ultra-high precision detection of target analytes; Preferably, the target analyte comprises an antibiotic; Preferably, the detection method comprises the following steps: The bovine serum albumin conjugate of antibiotic small molecule D was modified on the surface of the prism, denoted as D-BSA, as a biorecognition element; A solution of monoclonal antibody D-mAb containing antibiotic small molecule D is prepared; The antibiotic small molecule D in the sample competes with D-BSA and D-mAb for binding, wherein the amount of D-BSA modified on the prism surface and the amount of D-mAb in the solution are kept constant; The concentration of antibiotic small molecule D in the sample is quantitatively detected by measuring the signal change generated by the change in the specific binding amount of D-mAb and D-BSA.

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